Journal
BRIEFINGS IN BIOINFORMATICS
Volume 22, Issue 4, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bib/bbaa342
Keywords
Dppa2/4; zygotic genome activation; CG-rich region; decisive signaling pathways; Alppl2
Funding
- National Nature Scientific Foundation of China [62061034, 61702290, 61861036]
- Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region [NJYT-18-B01]
- Fund for Excellent Young Scholars of Inner Mongolia [2017JQ04]
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Dppa2 and Dppa4 cooperatively regulate cell pluripotency, transcriptional regulation, and ZGA. Overexpression of Dppa2/4 can make induced pluripotent stem cells closer to ESCs. Dppa2/4 activate signaling pathways by binding on CG-rich region of proximal promoter, facilitating ZGA, including Hippo, MAPK and TGF-beta signaling pathways.
Developmental pluripotency-associated 2 (Dppa2) and developmental pluripotency-associated 4 (Dppa4) as positive drivers were helpful for transcriptional regulation of zygotic genome activation (ZGA). Here, we systematically assessed the cooperative interplay of Dppa2 and Dppa4 in regulating cell pluripotency and found that simultaneous overexpression of Dppa2/4 can make induced pluripotent stem cells closer to embryonic stem cells (ESCs). Compared with other pluripotency transcription factors, Dppa2/4 can regulate majorities of signaling pathways by binding on CG-rich region of proximal promoter (0-500 bp), of which 85% and 77% signaling pathways were significantly activated by Dppa2 and Dppa4, respectively. Notably, Dppa2/4 also can dramatically trigger the decisive signaling pathways for facilitating ZGA, including Hippo, MAPK and TGF-beta signaling pathways and so on. At last, we found alkaline phosphatase, placental-like 2 (Alppl2) was completely silenced when Dppa2 and 4 single- or double-knockout in ESC, which is consistent with Dux. Moreover, Alppl2 was significantly activated in mouse 2-cell embryos and 4-8 cells stage of human embryos, further predicted that Alppl2 was directly regulated by Dppa2/4 as a ZGA candidate driver to facilitate pre-embryonic development.
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